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Trial registered on ANZCTR


Registration number
ACTRN12615001238561
Ethics application status
Approved
Date submitted
19/08/2015
Date registered
12/11/2015
Date last updated
1/11/2019
Date data sharing statement initially provided
1/11/2019
Date results information initially provided
1/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cardiac Magnetic Resonance Imaging and echocardiography in the detection of cardiotoxicity in cancer patients: A feasibility study
Scientific title
To determine the feasibility of cardiac MRI, echocardiography and serum biomarkers in detecting both early and later cardiac dysfunction in cancer patients after exposure to chemotherapy and/or radiotherapy.
Secondary ID [1] 287304 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
CARDIAC MRI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac dysfunction 295940 0
Breast Cancer 296000 0
Intra-thoracic cancer 296001 0
Lymphoma 296002 0
leukaemia 296003 0
Oesophageal cancer 296004 0
Chemotherapy related toxicity 296005 0
Radiotherapy related toxicity 296006 0
Condition category
Condition code
Cardiovascular 296205 296205 0 0
Normal development and function of the cardiovascular system
Cardiovascular 296285 296285 0 0
Other cardiovascular diseases
Cancer 296286 296286 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To perform MRI, echocardiograms and serum biomarkers at pre-treatment and post-treatment time points for detection of cardiac dysfunction. Each test is an addition to standard care.
The study echocardiograms and cardiac MRI scans and serum biomarkers as outlined above will be performed at
1) baseline prior to commencement of any chemotherapy or radiotherapy, then at 2) 6-8 weeks post radiotherapy and then again at approximately 12 months after completion of
the last active cancer treatment (either chemotherapy or radiotherapy). Patients from Cohorts A to C inclusive undergoing chemotherapy prior to radiotherapy, will have their study-related imaging performed at a 2-3 week interval post chemotherapy. Patients will thus undergo a minimum of 2 and a maximum of 4 echocardiograms and cardiac MRI scans (pre and post chemotherapy, and/or pre and post radiotherapy), depending on the patient’s cancer treatment program.
For each MRI scan, the patient will lay still on a flat bed which moves through a cylindrical tunnel scanner. The scan will take approximately 20 minutes.
For each echocardiogram, the patient will undergo an ultra-sound test laying on a bed, and can take approximately 20 minutes.
At each study time-point, cardiac toxicity will be documented by the study clinicians by taking a directed cardiac history, examination, and scoring toxicity as per the
Common Terminology Criteria for Adverse Events V4 grading system, and NYHA score.
All appointments will be captured and noted on the patient's electronic medical record at their hospital.
Serum biomarker testing involves bloods sample taken and analysed in a laboratory.
Intervention code [1] 292627 0
Early detection / Screening
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295880 0
To determine the feasibility of cardiac MRI and heart ultrasound in detecting both early and later cardiac dysfunction in breast and intra-thoracic cancer patients after exposure to chemotherapy and/or radiotherapy.

Comparisons of echocardiography with cardiac MRI with routine GHPS (documenting
LVEF) performed pre-chemotherapy, at each of these time points will be undertaken.
[composite primary outcome 1]
Timepoint [1] 295880 0
Baseline and early i.e. 6-8 weeks post radiotherapy completion, and later, i.e. up to 12 months after exposure to cardiotoxic chemotherapy and/or local radiotherapy.
Secondary outcome [1] 316807 0
To assess the relative contributions of both cardiotoxic chemotherapy and local radiotherapy on cardiac function as determined by cardiac MRI and 2D/3D echocardiography.
Timepoint [1] 316807 0
Baseline and early i.e. 6-8 weeks post radiotherapy completion, and later, i.e. up to 12 months after exposure to cardiotoxic chemotherapy and/or local radiotherapy.
Secondary outcome [2] 316962 0
To compare left ventricular function, myocardial tissue and characterize cardiac and vascular dysfunction as determined by the two imaging modalities of cardiac MRI and 2D/3D echocardiography.
This is a composite secondary outcome
Timepoint [2] 316962 0
Baseline and early i.e. 6-8 weeks post radiotherapy completion, and later, i.e. up to 12 months after exposure to cardiotoxic chemotherapy and/or local radiotherapy.
Secondary outcome [3] 316963 0
To attempt to correlate any changes in cardiac function as determined by cardiac MRI and 2D/3D echocardiography with the participant’s clinical cardiac symptoms, cumulative chemotherapy doses, and radiation dose/volume parameters.
Timepoint [3] 316963 0
Baseline and early i.e. 6-8 weeks post radiotherapy completion, and later, i.e. up to 12 months after exposure to cardiotoxic chemotherapy and/or local radiotherapy.
Secondary outcome [4] 317235 0
Cardiac serum biomarkers of Troponin and BNP are measured to evaluate heart function to help diagnose heart diseases and conditions.
Timepoint [4] 317235 0
Baseline and early i.e. 6-8 weeks post radiotherapy completion, and later, i.e. up to 12 months after exposure to cardiotoxic chemotherapy and/or local radiotherapy.

Eligibility
Key inclusion criteria
Cohort A – breast cancer patients

(i) Aged greater than or equal to 18 years or older
(ii) Histologically confirmed diagnosis of invasive breast carcinoma
(iii) Receiving any anthracycline-containing breast cancer treatment regimen, including any adjuvant trastuzumab therapy AND going on to receive adjuvant left breast +/- loco-regional nodal radiotherapy, OR
(iv) Receiving adjuvant left breast +/- loco-regional nodal radiotherapy alone (without chemotherapy).

Acceptable radiotherapy regimens for Cohort A patients include:
a)50Gy in 25 daily fractions +/- 10-16Gy tumour bed boost, over 5-6 weeks
b)42.4Gy in 16 daily fractions +/- 10Gy tumour bed boost, over 3-4 weeks

Cohort B – Non Hodgkin (NHL) Hodgkin lymphoma (HL) and leukaemia patients
(i) Aged greater than or equal to 18 years or older
(ii) Histologically confirmed diagnosis of lymphoma
(iii) Receiving any anthracycline-or alkylator-containing chemotherapy regimen (eg. R-CHOP for NHL patients and ABVD for HL patients) and/or
(iv) Receiving definitive or adjuvant (post-chemotherapy) radiotherapy (dose greater than or equal to 20Gy) encompassing the mediastinum (ie. including cardiac structures)

Acceptable radiotherapy regimens for Cohort B patients include:
*Dose ranges from 20-40Gy in 1.5-2Gy daily fractions, over 2-4 weeks

Cohort C – other intra-thoracic/upper gastrointestinal malignancy patients (eg oesophageal/other eg thymoma)
(i) Aged greater than or equal to 18 years or older
(ii) Histologically confirmed intra-thoracic or upper gastrointestinal malignancy
(iii)Receiving any neoadjuvant - and/or adjuvant or concurrent chemotherapy regimen and
(iv)Receiving definitive or adjuvant radiotherapy (dose greater than or equal to 20Gy) encompassing the mediastinum (ie including cardiac structures)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) any contraindication to cardiac MRI (i.e. shrapnel, metallic implants/clips, pacemaker or defibrillator);
(ii) severe claustrophobia;
(iii) an estimated glomerular filtration rate of less than 50 mL/min/1.732;
(iv) pregnancy or breast feeding;
(v) documented distant metastases from their known primary cancer;
(vi) patients receiving cancer treatment with palliative intent
(vii) planned or current use of other targeted biological therapies that can potentially cause cardiotoxicity (i.e. lapatinib)
(viii) Pre-existing symptomatic Heart Failure (NYHA Class III or IV).
(ix) Recent acute coronary syndrome (myocardial infarction, unstable angina) within the last six months
(x) Recent coronary revascularization (percutaneous coronary intervention or coronary bypass surgery) within six months
(xi) Permanent atrial fibrillation
(xii) Prosthetic breast implants that preclude echocardiography examination

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4224 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 10196 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 291872 0
Other Collaborative groups
Name [1] 291872 0
Ingham Institute Breast Cancer Grant
Address [1] 291872 0
SWSLHD Area Cancer Services, Locked Bag 7103, Liverpool BC, NSW 1871, Australia
Country [1] 291872 0
Australia
Primary sponsor type
Hospital
Name
Liverpool Hospital
Address
SWSLHD Area Cancer Services Locked Bag 7103, Liverpool BC, NSW 1871, Australia
Country
Australia
Secondary sponsor category [1] 290536 0
None
Name [1] 290536 0
Address [1] 290536 0
Country [1] 290536 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293385 0
South Western Sydney Local Health District
Ethics committee address [1] 293385 0
Locked Bag 7103 Liverpool BC NSW 1871
Ethics committee country [1] 293385 0
Australia
Date submitted for ethics approval [1] 293385 0
Approval date [1] 293385 0
16/03/2015
Ethics approval number [1] 293385 0
HREC/14/LPOOL/531

Summary
Brief summary
The primary purpose of this study is to determine the feasibility of using cardiac MRI scans, cardiac ultrasound and blood tests to detect changes in heart function following completion of chemotherapy and/or radiation therapy for cancer. Who is it for? You may be eligible to join this study if you are aged 18 or over, and have been diagnosed with breast cancer, Hodgkin's lymphoma, Non-Hodgkin's lymphoma, leukaemia or other intra-thoracic/upper gastrointestinal malignancies such as cancer of the oesophagus or thymoma, for which chemotherapy and/or radiotherapy have been prescribed. Study details All participants in this study will undergo additional cardiac screening tests at timepoints before and after chemotherapy/radiation therapy up to 12 months following the end of therapy. These tests will include MRI scans, cardiac ultrasound scans and blood samples being taken. Results from these tests will be used to assess changes in cardiac function caused by the cancer therapy. It is hoped that the findings of this feasibility trial will ultimately aid early identification of heart injury due to cancer therapy, and thus enable prevention strategies and early treatment options in these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59622 0
Dr Eng-Siew Koh
Address 59622 0
Locked Bag 7103 Liverpool BC NSW 1871
Country 59622 0
Australia
Phone 59622 0
+61 2 8738 9806
Fax 59622 0
Email 59622 0
eng-siew.koh@health.nsw.gov.au
Contact person for public queries
Name 59623 0
Ms Penny Phan
Address 59623 0
Locked Bag 7103 Liverpool BC NSW 1871
Country 59623 0
Australia
Phone 59623 0
+61 2 8738 9148
Fax 59623 0
+61 2 8738 9205
Email 59623 0
penny.phan@health.nsw.gov.au
Contact person for scientific queries
Name 59624 0
Dr Simon Tang
Address 59624 0
Locked Bag 7103 Liverpool BC NSW 1871
Country 59624 0
Australia
Phone 59624 0
+61 2 8738 3000
Fax 59624 0
Email 59624 0
Simon.tang@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 5529 0
S. Tang, J. Otton, L. Holloway, G Delaney, A. George, M. Jameson, D. Tran, V. Batamulai, L. Thomas, ES. Koh; Quantification of cardiac subvolume dosimetry using a 17 segment model of the left ventricle in breast cancer patients receiving tangential beam radiotherapy; Radiotherapy and Oncology 2019; 132:257-265
Publication: 2019
Attachments [1] 5529 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary